The present invention relates to a pharmaceutical preparation comprising a fat emulsion of fat microparticles.
In recent years there have been attempted to use, as a drug carrier for a fat-soluble medicinal compound, fat particles in fat emulsion which has been therapeutically employed as a neutritional support for patients after an operation. In conventional fat emulsion for supplying nutrition, however, even relatively small fat particles have a mean particle diameter of as large as 200 nm have been used. When fat particles having such a large particle diameter are used for a pharmaceutical preparation comprising fat particles containing a medicinal compound, the pharmaceutical preparation is, when administered, mostly uptaken by reticuloendothelial system such as liver and spleen, and therefore, the medicinal compound cannot be delivered to a desired site. So, it has been attempted to use fat microparticles so that they may not be uptaken by reticuloendothelial system and the medicinal compound may be delivered to the desired site. As such pharmaceutical preparation comprising a fat emulsion of fat microparticles, there have been known, for example, a fat emulsion of fat microparticles having a mean particle diameter of 40 nm to 70 nm which contain a benzo[a]phenazine anticancer drug (Japanese Unexamined Patent Publication No. 143834/1989) and a fat emulsion of fat microparticles having a mean particle diameter of 10 nm to 40 nm which contain a fat-soluble medicinal compound (Japanese Unexamined Patent Publication No. 249716/1989).
However, in a system containing microparticles, their particle diameter tends to increase with a lapse of time owing to the flocculation or coalescence thereof. Therefore, it has been difficult to obtain a long-term stable pharmaceutical preparation comprising a fat emulsion of fat microparticles.
From the viewpoint of handling, transportation and storage in a practical use of a pharmaceutical preparation, a pharmaceutical preparation comprising a fat emulsion of fat microparticles which can be stored usually as the lyophilized pharmaceutical preparation and can be easily reconstituted into the pharmaceutical preparation comprising a fat emulsion of stable fat microparticles by adding a solvent such as distilled water for injection before using, will be extremely advantageous. However, it has been very difficult to obtain such a pharmaceutical preparation.
An object of the invention is to provide a pharmaceutical preparation comprising a fat emulsion of fat micropaticles, which can be usually stored for a long period as a lyophilized product and can be easily reconstituted into the pharmaceutical preparation comprising a fat emulsion of stable fat microparticles by adding a solvent such as water, by which pharmaceutical preparation, a medicinal compound can be retained in the blood without being uptaken by the reticuloendothelial system.
This and other objects of the present invention will become apparent from the description hereinafter.